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  1. Perceived Illness and Treatment Adherence to Hypertension Among Patients Attending a Tertiary Hospital in Kathmandu, Nepal
    Shakya R, Shrestha S, Gautam R, Rai L, Maharjan S, Satyal GK, et al.
    Patient Prefer Adherence, 2020;14:2287-2300.
    PMID: 33244224 DOI: 10.2147/PPA.S270786
    Introduction: Hypertension (HTN) is a silent killer, accountable for life-threatening complications. An individual's illness perception may affect adherence to treatment which is crucial to prevent complications of HTN. The objective of this study was to identify illness perception and treatment adherence among patients with HTN in a tertiary hospital in Kathmandu, Nepal.

    Methods: Descriptive correlational study was conducted in the out-patient department of Manmohan Cardiothoracic Vascular and Transplant Center, Kathmandu Nepal. Non-probability purposive sampling was used. A face-to-face interview was conducted from September to December 2018, using a structured questionnaire that included socio-demographic variables, illness perception questionnaire (revised) and Hill bone compliance to high blood pressure therapy scale. Data analysis was done by using descriptive and inferential statistics (chi-square test, Spearman rank correlation).

    Results: Among 204 participants, 51% were male, 77% were literate, mean ± S.D. age was 60±12. About 72% experienced headache and 88% said that headache is related to HTN. Behavioural factors and psychological factors were regarded as the leading cause of HTN. Almost 63% participants believed HTN as highly threatening illness. Higher scores in timeline (acute/chronic), personal control, and treatment control revealed that patients believed HTN as a chronic disease with a higher rate of personal and treatment control. Regarding treatment adherence, the mean score was 16.58 (SD = 2.08), and only 14.7% had perfect adherence. Participants were more adherent to medication and appointment keeping rather than reduce salt intake. Duration of HTN diagnosis (p=0.027) and duration under HTN medication (p= 0.021) were found to be significantly associated with treatment adherence. There was a significant positive correlation between illness perception and treatment adherence (ρ = 0.282, p<0.01).

    Conclusion: Illness perception and treatment adherence are correlated. Hence, it is beneficial to improve illness perception to achieve perfect treatment adherence. Reinforcement is essential to maintain adherence to both medications and behaviour therapy.

  2. Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer
    Shakya R, Tarulli GA, Sheng L, Lokman NA, Ricciardelli C, Pishas KI, et al.
    Oncogene, 2017 08;36(31):4469-4480.
    PMID: 28368395 DOI: 10.1038/onc.2017.66
    Missense mutations in the TP53 tumor-suppressor gene inactivate its antitumorigenic properties and endow the incipient cells with newly acquired oncogenic properties that drive invasion and metastasis. Although the oncogenic effect of mutant p53 transcriptome has been widely acknowledged, the global influence of mutant p53 on cancer cell proteome remains to be fully elucidated. Here, we show that mutant p53 drives the release of invasive extracellular factors (the 'secretome') that facilitates the invasion of lung cancer cell lines. Proteomic characterization of the secretome from mutant p53-inducible H1299 human non-small cell lung cancer cell line discovered that the mutant p53 drives its oncogenic pathways through modulating the gene expression of numerous targets that are subsequently secreted from the cells. Of these genes, alpha-1 antitrypsin (A1AT) was identified as a critical effector of mutant p53 that drives invasion in vitro and in vivo, together with induction of epithelial-mesenchymal transition markers expression. Mutant p53 upregulated A1AT transcriptionally through the involvement with its family member p63. Conditioned medium containing secreted A1AT enhanced cell invasion, while an A1AT-blocking antibody attenuated the mutant p53-driven migration and invasion. Importantly, high A1AT expression correlated with increased tumor stage, elevated p53 staining and shorter overall survival in lung adenocarcinoma patients. Collectively, these findings suggest that A1AT is an indispensable target of mutant p53 with prognostic and therapeutic potential in mutant p53-expressing tumors.
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